Priorities in Liver Disease Research - Past, Present, and Future - Jay Hoofnagle

Transcript

• 00:19Welcome back to the Yale Liver
• 00:22Diamond Jubilee. This session
• 00:23is being recorded. Thank you.
• 00:29Well, welcome to everyone and
• 00:32and our next week is the is
• 00:34going to be Doctor Jay Hufnagel.
• 00:36Dr Hufnagel is director of liver disease
• 00:39research branch at NIDDK and also
• 00:41proud Yale School of Medicine alone
• 00:44and the title of this talk will be
• 00:46priorities and liver disease research.
• 00:48Past present and future and IDK
• 00:51perspective Jay please go ahead.
• 00:59OK, well thank you.
• 01:00I'm sorry I can't be there in person
• 01:02and they have to do this virtually.
• 01:06I'm going to talk about.
• 01:08NIH liver disease funding.
• 01:12The the past,
• 01:13the present and the future.
• 01:17This is the present at the present time.
• 01:22The amount of liver disease research
• 01:25funding at the NIH is $845 million.
• 01:29It's about 2% of the NIH budget.
• 01:31This slide shows you the
• 01:33breakdown by institute.
• 01:35Of the 26 institutes at the NIH,
• 01:38many of them fund liver disease research
• 01:40in IDK has the largest proportion.
• 01:43It's about 33%.
• 01:45The NCI is also an important contributor,
• 01:48as is NIAID, the allergy and
• 01:51Infectious Disease Institute,
• 01:52and the Alcohol Institute.
• 01:56That's. That's the present.
• 02:00This is a N IDK structure.
• 02:02We have 3 extramural divisions that
• 02:05fund grants in research, diabetes,
• 02:08adjustive disease and nutrition and kidney,
• 02:12urology, hematology.
• 02:13They are similar in size,
• 02:15diabetes, a little bit larger.
• 02:18The liver disease research
• 02:20branches within the digestive
• 02:22disease and nutrition division.
• 02:24In addition,
• 02:25I DK has intramural program that
• 02:28means on campus and in the intramural
• 02:31program is the liver diseases branch.
• 02:33I started there at the NIH in
• 02:35the liver diseases branch.
• 02:37At the time it was the smallest branch.
• 02:40And IDK.
• 02:41It is now the largest branch.
• 02:45And in 1988 I left the liver disease
• 02:48branch to become the head of the
• 02:51digestive disease and nutrition division.
• 02:54But I've kept my involvement there.
• 02:58And this, as a chairman of the director
• 03:01of the of the Digestive Disease and
• 03:04Nutrition Division I had an Advisory
• 03:06Council Advisory Council to the Institute.
• 03:09We have 4 senior members experts who.
• 03:13Or advisors to in gastroenterology
• 03:15Sid Cohen and Jerry Trier,
• 03:18one in nutrition, George Pray.
• 03:20And this young man, representing liver,
• 03:23who I remembered from liver from Gale,
• 03:26the first liver biopsy I ever saw,
• 03:29was being done by Jim Boyle.
• 03:32Also important behind me are
• 03:33the staff and I want to show you
• 03:36the liver diseases branch at the
• 03:37time as this person right here.
• 03:39Sarah kauser.
• 03:40She took care of all of the liver
• 03:43disease research portfolio.
• 03:47So that's where we began many years
• 03:50ago and our. Budget was $43 million.
• 03:52That was a lot of the time I thought.
• 03:58Now I go to the the present.
• 04:00Here is the liver disease branch,
• 04:02but the present and our.
• 04:05Amount of money has.
• 04:08Increased sixfold to 200 about 250.
• 04:13And our staff has increased about 6
• 04:16fold as well. We now have six other
• 04:20members of the branch of Bonnie.
• 04:23Those views who I hope you know she's
• 04:26in charge of our basic programs.
• 04:28Edward do and April Sherker 2
• 04:31transplant Hepatologist who run at
• 04:33some of our categorical branches.
• 04:38This is Jose Serrano is an
• 04:40MD PhD gastroenterologist.
• 04:42He runs the pancreas program and
• 04:44part of the liver disease branch,
• 04:46and here are two new faces.
• 04:48Actually, they're so new that I
• 04:50haven't met with them in person.
• 04:51We've only talked on zoom about
• 04:54weekly about one at least once.
• 04:56Weekly. One is Katrina Lowe.
• 04:58She is a pediatric gastroenterologist.
• 05:02Hepatologist, her true love is hepatology,
• 05:05and she's taking over some
• 05:07of our pediatric programs,
• 05:08and this is Ludmilla Polanski,
• 05:12who is a PhD geneticist who
• 05:15has joined us from UC San.
• 05:18San Francisco also has done research
• 05:22in the genetics of liberties.
• 05:25These two new people are joined.
• 05:28The division in general,
• 05:29and they have some GI components
• 05:31not shown in this picture.
• 05:33As a as a person who has just joined us,
• 05:35who is an expert on the microbiome.
• 05:38So as the field grows,
• 05:40the staff has grown in the
• 05:42liver disease branch.
• 05:45Overseas branch actually
• 05:46was a was added to an IDK.
• 05:49In 2003 it was created on on the basis of
• 05:52congressional language to promote liver
• 05:55disease related research across the NIH.
• 05:59We were charged to develop an action
• 06:01plan for liver disease research.
• 06:03And to manage the portfolio as well
• 06:06as to represent the NIH broadly
• 06:09in liver disease issues.
• 06:11Here's the action plan that
• 06:13we published in 2004.
• 06:14Many of you participated in helping out,
• 06:17including the Michael Nathanson
• 06:19and John Boyer.
• 06:20To put this together.
• 06:22What we did is I I took all the grants funded
• 06:26by the NIH that were coded as liver related,
• 06:30not just our our institute,
• 06:33but all institutes and I put them into piles.
• 06:36I I started with 12 piles but it expanded
• 06:40to 16 topic areas which I show here.
• 06:43Now the first four called basic,
• 06:45but they're not all of the grants are basic.
• 06:47Almost all of these grants were basic.
• 06:49Very few clinical grants.
• 06:51These, however, are.
• 06:54Are nonspecific?
• 06:56I should say they refer to the
• 06:58liver in general and not to a
• 07:00specific disease or condition.
• 07:02Selling molecular biology,
• 07:03for instance,
• 07:04is what Mike Nathanson has his grants
• 07:06in bio Billy Ruben Cholestasis.
• 07:08Sounds like Jim Boyer, doesn't it?
• 07:11These were our largest thing.
• 07:15Portfolio here's the breakdown I made
• 07:19on the basis of these 16 areas and
• 07:23shown in each is the the institutes of
• 07:26that are involving say DK shown and red.
• 07:29We were the major participants of major
• 07:33contributors to the basic portfolio.
• 07:35And barrel hepatitis.
• 07:36We actually only represent about 10%.
• 07:38The majority was by NIIT and
• 07:41by what's called NCRR.
• 07:43That's research resources.
• 07:45This is currently known as incats.
• 07:50Fatty liver disease very little from us,
• 07:52mostly from the Alcohol Institute.
• 07:54Drug induced liver disease, mostly from
• 07:57environmental health and of course,
• 07:58cancer, almost entirely by cancer.
• 08:03So while we represented only about
• 08:051/3 of funding for liver disease,
• 08:09we represent the areas that we think.
• 08:12Of as being liver most most importantly.
• 08:18Here's the breakdown by the grants
• 08:21that were administered by us and
• 08:24delivered disease research branch.
• 08:26You can see the basic program
• 08:28represented the majority of
• 08:29more than half of the grants.
• 08:31In 2004 we had 162 grants that were.
• 08:36Now let's the past to the present by
• 08:40showing green the distribution of
• 08:43grants now 364 by these topic areas.
• 08:46So the number of grants that
• 08:48we fund is more than doubled.
• 08:50And has increased in virtually all
• 08:52of the all of the topic areas.
• 08:54Some more than others,
• 08:55and of course the one that's expanded
• 08:58enormously is in fatty liver disease.
• 09:00We had two grants.
• 09:032014 88. It's kind of overburdening,
• 09:06and we're going to have to divide it in half.
• 09:10At two runs, this program and our
• 09:12one of our new people will have
• 09:14to take some of this from him.
• 09:16Shows you what's happened in liver disease.
• 09:21Now, what about money?
• 09:23Now we're talking Turkey huh?
• 09:25So here I show you the growth of the NIH
• 09:29total budget in green with the red dots.
• 09:32As well as the growth of.
• 09:35Total liver funded grants across the NIH.
• 09:40Shown in the.
• 09:42Between 1993 and 2009.
• 09:47And you can see the NIH budget was.
• 09:51Flat for many years,
• 09:53but then began to increase,
• 09:54and during this very important period here,
• 09:57the Senate doubled the NIH budget.
• 10:01You can see the liver component
• 10:03of the NIH has increased a
• 10:05little bit ahead of the curve.
• 10:07Actually,
• 10:08a lot ahead of the curve and this really
• 10:10started with the doubling of the budget.
• 10:12Come back to that 2009.
• 10:15I cut off there,
• 10:16not at the president because in 2009
• 10:18something very important happened
• 10:19and that is the coding of grants
• 10:21was taken away from the Institute.
• 10:23Each institute did it separately
• 10:25and it was very variable and it
• 10:28was done by computer after that.
• 10:31That that caused an immediate increase in
• 10:34liver related funding by over $100 million.
• 10:38So what I've done is I've
• 10:39taken the balance back.
• 10:41Baseline of 2009.
• 10:44After this coding and these are
• 10:47data based on what's called RCDC,
• 10:49the coding things shows that
• 10:51our budget has been fairly
• 10:53flat for the first six years,
• 10:55but has increased over the last
• 10:57six or seven years and again,
• 11:00liver disease a little bit
• 11:01ahead of the curve.
• 11:07So that's mostly basic research.
• 11:10What about clinical research?
• 11:11Clinical research was really benefited
• 11:13by the doubling of the budget,
• 11:15because during this doubling
• 11:17we were able to create what we
• 11:19call clinical research networks,
• 11:21and we created quite a few.
• 11:23Initially, the HALLSEY trial
• 11:25acute liver failure Study group.
• 11:28Byron Upsy PC big big pressure
• 11:31on big look at C,
• 11:33but you can see that stopped and
• 11:35what we've done is as time goes on,
• 11:38we've changed the the types of clinical
• 11:41research networks that we've done.
• 11:43One of the longest standing ones
• 11:45is the Nash and this one here that
• 11:48is children now call children,
• 11:50began as the bill area tree
• 11:52show research network.
• 11:54Some have been in liver transplantation
• 11:56and acute liver failure.
• 11:58But you see,
• 11:59some after a while they stopped after
• 12:01either 5 to 10 or even 20 years.
• 12:07And currently we have 3 being funded,
• 12:10the hepatitis B research network
• 12:12has technically ended their funding
• 12:14there in a no cost extension.
• 12:17Here we are in 2022 and we've had two
• 12:20new clinical research networks added.
• 12:26The first of these is called triumph.
• 12:28This is actually investigator
• 12:31initiated by Estella Alonso.
• 12:33Who was Valerie dukowski?
• 12:35Our the statistician has created this
• 12:38network of 20 different centers across
• 12:41the United States that are participating
• 12:44in a randomized controlled trial of
• 12:48comparing antithymocyte globulin.
• 12:50To high dose Methylprednisolone.
• 12:53People sibo and children with acute
• 12:56liver failure of unknown cause.
• 12:59Despite 20 years of looking,
• 13:01we have not been able to sort
• 13:03out what the cause of acute
• 13:05liver failure is in children,
• 13:07and about 40% of cases.
• 13:11The cytokine look at these children
• 13:13appears to show that they have increased
• 13:16signal interferon signaling and a lot
• 13:19of this trial is focused on studying
• 13:23the immune mediated pathophysiology.
• 13:25So that's triumph. It's just started.
• 13:27Actually patients have not been enrolled yet.
• 13:29I believe Yale is one of the centers
• 13:32that are participating in Trump.
• 13:34This is the other network that we created
• 13:37last year that's still being formulated,
• 13:39and that's the liver cirrhosis network
• 13:41that consists of 10 clinical centers
• 13:44across the United States and the data
• 13:46coordinating Center at Northwestern.
• 13:48They are currently putting together a
• 13:51cohort study of patients to be followed
• 13:53with cirrhosis and a statin intervention
• 13:56trial and somewhat similar to the VA
• 13:59trial that Lupe presented recently.
• 14:02This group has just gotten together.
• 14:04We don't even have a logo yet, but.
• 14:08As part of the.
• 14:09We are also involved in strategic planning
• 14:12and here are three examples of that.
• 14:14Here's the strategic plan from our institute.
• 14:17It's a broad based plan that
• 14:20includes a liver disease.
• 14:22Here's an important plan and
• 14:25hepatitis BA search for the cure.
• 14:29It's going to be a long search I'm afraid,
• 14:31but that's what it's aimed at and
• 14:32this is a strategic plan that's
• 14:34actually just now being written
• 14:36and finally a strategic plan for
• 14:38elimination of viral hepatitis.
• 14:40This is government wide and our branch has
• 14:44has has led the NIH participation in that.
• 14:49Another important area for
• 14:51priorities for the future,
• 14:53or is this issue of inclusion,
• 14:56diversity, equity and accessibility.
• 14:59What's called IPO? To which our
• 15:02institute has has added civility.
• 15:03I'm not sure what civility means.
• 15:05It's a little bit.
• 15:07But what this is is expanding participation
• 15:10of women and underrepresented
• 15:13minorities in our research,
• 15:16not just the staff but also investigators.
• 15:20This is ongoing and is just starting up,
• 15:24but it's it's going to be an
• 15:26important part of the future.
• 15:28Here are some research opportunities
• 15:30that we've published in the last year.
• 15:32What I think should be applicable to Yale
• 15:36Center one is a program announcement.
• 15:39So actually have set review times and
• 15:42there is some set aside money, very exciting.
• 15:45One early stage.
• 15:46Preclinical validation of therapeutic leads.
• 15:49This is being led by Bonnie
• 15:51Burgess because and.
• 15:54Take a look at it.
• 15:56Early stage and here is the important
• 15:59announcement about high impact
• 16:01interdisciplinary science, the RC2,
• 16:04the RC2 is a somewhat new mechanism.
• 16:08It is basically replacing
• 16:10the program project slowly.
• 16:12Program projects are largely being
• 16:15wound down and this is a very exciting
• 16:18mechanism and it's aimed at innovation.
• 16:22Translational basic research.
• 16:26And finally a special interest
• 16:30announcement from our Institute on Sex,
• 16:33Gender, race, and ethnicity attempting
• 16:36to encourage grants in those areas.
• 16:39So here we are at the present of current
• 16:42NIH budget is $41 billion. That's all.
• 16:47And IDK budget is about $2.1 billion.
• 16:53Again, this is 2002.
• 16:54We're Aussie a year or two behind
• 16:56and and being able to show
• 16:57you what the budget really is.
• 16:59Liver disease reach our research funding at
• 17:04845 million per year.
• 17:05About 2% of the NIH budget.
• 17:08And and and IDK about 245 million.
• 17:12It's about 12% of the NTK budget.
• 17:17So that's the mostly the
• 17:19past and the present.
• 17:20I can't really tell you what
• 17:22the future is going to be,
• 17:23but we are very committed
• 17:25to continuing a healthy.
• 17:26A healthy stimulation of
• 17:29liver disease research.
• 17:30Thank you.
• 17:32Yeah. Doctor Hoofnagle,
• 17:33thanks very much for her brutal
• 17:36review and in highlighting some
• 17:39granting opportunities for us.
• 17:41Thank you very much.
• 17:44Welcome.